Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation.

Antibody responses develop following SARS-CoV-2 infection, but little is known about their epitope specificities, clonality, binding affinities, epitopes, and neutralizing activity. We isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject 21 days after the onset of clinical disease. 45 S-specific monoclonal antibodies were generated. They had undergone minimal somatic mutation with limited clonal expansion, and three bound the receptor-binding domain (RBD). Two antibodies neutralized SARS-CoV-2. The most potent antibody bound the RBD and prevented binding to the ACE2 receptor, while the other bound outside the RBD. Thus, most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 S-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive and/or therapeutic potential and can serve as templates for vaccine design.
Competing Interests: Declaration of Interests The authors declare no competing financial interests. A provisional patent application (U.S. Provisional Application No. 63/016268) has been filed on the SARS-CoV-2 specific monoclonal antibodies isolated herein. H.Y.C. receives personal fees from Merck (consultant), personal fees from Glaxo Smith Kline (consultant), grants from Sanofi-Pasteur, non-financial support from Cepheid, non-financial support from Ellume, and non-financial support from Genentech. The content of these consultancies and support are unrelated to the work performed in this manuscript.
(Copyright © 2020 Elsevier Inc. All rights reserved.)